Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2).
BACKGROUND
This article is focused on platelet-activating factor acetylhydrolase (PAF-AH), a lipoprotein bound, calcium-independent phospholipase A(2) activity also referred to as lipoprotein-associated phospholipase A(2) or PLA(2)G7. PAF-AH catalyzes the removal of the acyl group at the sn-2 position of PAF and truncated phospholipids generated in settings of inflammation and oxidant stress.


CONCLUSIONS
Here, I discuss current knowledge related to the structural features of this enzyme, including the molecular basis for association with lipoproteins and susceptibility to oxidative inactivation. The circulating form of PAF-AH is constitutively active and its expression is upregulated by mediators of inflammation at the transcriptional level. This mechanism is likely responsible for the observed up-regulation of PAF-AH during atherosclerosis and suggests that increased expression of this enzyme is a physiological response to inflammatory stimuli. Administration of recombinant forms of PAF-AH attenuate inflammation in a variety of experimental models. Conversely, genetic deficiency of PAF-AH in defined human populations increases the severity of atherosclerosis and other syndromes. Recent advances pointing to an interplay among oxidized phospholipid substrates, Lp(a), and PAF-AH could hold the key to a number of unanswered questions.
Stafforini
Diana M
DM
Huntsman Cancer Institute and Department of Internal Medicine, University of Utah, 2000 Circle of Hope, Suite 3364, Salt Lake City, UT 84112-5550, USA. diana.stafforini@hci.utah.edu
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D017270:Lipoprotein(a) / Q000378:metabolism; D018384:Oxidative Stress; D012720:Severity of Illness Index; D015854:Up-Regulation
D018836:Inflammation Mediators; D017270:Lipoprotein(a); D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase